1990 Fiscal Year Final Research Report Summary
In Vitro New Evaluation Method for the Drug Absorption and Secretion Using Membrane Vesicles
| Project/Area Number |
01870112
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Medical and Dental University (1990)
Kyoto University (1989) |
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Principal Investigator |
INUI Kenーichi Tokyo Medical and Dental University, School of Medicine, Department of Hospital Pharmacy, Professor, 医学部, 教授 (70034030)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Hideyuki Tokyo Medical and Dental University, School of Medicine, Department of Hospital, 医学部, 助手 (40225727)
TAKANO Mikihisa Kyoto University, Faculty of Medicine, Department of Hospital Pharmacy, Instruct, 医学部, 助手 (20211336)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Intestinal Absorption / Tubular Secretion / BrushーBorder Membrane / Membrane vesicle / Organic Anion / Organic Cation / betaーLactam Antibiotic / Dipeptide Transport System |
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| Research Abstract |
The absorptive and secretory processes play important roles for the drug disposition in the body. These processes imply sum of the transport phenomena across cell membranes, and are often regulated by the active transport systems. In this study, we attempted to establish in vitro method for the evaluation of the drug absorption and secretion using membrane vesicles isolated from the renal and intestinal epithelial cells.
1. Transport in the intestinal brushーborder membranes and absorption : Aminoーbeta-lactam antibiotics was transported via a common transport system with dipeptides in the intestinal brushーborder membranes and the transport was driven by aninward H^+ gradient. A good correlation was found between the intestinal absorption rate and the initial uptake rate by brushーborder membrane vesicles. Bestatin, an antitumor agent, is a dipeptide containing an unusual amino acid, and is wellーabsorbed from the small intestine despite of it's low lipophilicity. Bestatin was also transported via the H^+ dipeptide cotransport system in the intestinal brushーborder membranes.
2. Transport in the renal tubular cell membranes and secretion : H^+/organic cation antiport system in the brush-border membranes contributed to the tubular secretion of cationic drugs such as cimetidine. Aminoーbeta-lactam antibiotics and ofloxacin, a pyridonecarboxylic acid derivative, also interacted with the H^+/organic cation antiport system, indicating an important role in the tubular secretion of those drugs. In Contrast, most beta-lactam antibiotics were transported via organic anion transport systems in the basolateral membranes. The present data suggest that the tubular aecretion of drugs can be estimated by the analysis of the drug interaction with organic ion transport systems using renal membrane vesicles.
In conclusion, membrane vesicles could be a useful screening system to evaluate the absorption and secretion of drugs.
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